Contractor: Department of Community and Environmental Medicine and the Irvine Occupational Health Center, UC Irvine

Contract Number: A6-203-33

Carbon monoxide (CO) reversibly reacts with proteins, competing with oxygen for binding sites on hemoglobin and myoglobin molecules, compromising the ability of these proteins to transport oxygen. Small decreases in hemoglobin oxygen-carrying ability resulting from 3 to 5% carboxyhemoglobin (COHb) levels can significantly reduce the ability of sensitive individuals to perform exercise; such effects have been documented over the past several years. Low-level CO exposure reduced the time to onset of angina in men with stable angina pectoris and reduced the maximum aerobic capacity achieved in normal individuals during exercise. There are, however, many areas of uncertainty in clinical studies of CO health effects. Among these are: the large amount of subject-to-subject variability in physiologic responses to CO; reported biases in the spectro -photometric methods used for measurement of COHb in blood in several previously reported studies; interactions between medications a subject takes for control of his angina and the response of that subject to CO; and high variability in rate of uptake of CO between subjects. The goal of this study was to improve methods to more accurately and reliably determine the subclinical effects of low-level CO exposure on cardiac function in individuals with ischemic heart disease. To accomplish this objective, we undertook development studies to improve the analytical chemical methodology for measuring low-level carboxyhemoglobin we evaluated additional potentially more sensitive endpoints and modified exposures and exercise test protocols for detecting CO-induced changes in the heart, and we established criteria to better characterize those subjects who were most 124~ to be sensitive to CO exposure under different environmental conditions. WC then integrated the results of our work and applied them to determine the feasibility of resting whether there was significant interaction between CO-induced hypoxia and hypoxia related to high altitude exposure. The latter point is based upon predictions of models which have not been validated by laboratory studies.